The purpose of the proposed research is to expand our understanding of the role of membranes and, in particular, specific membrane lipids during infection of human cells by herpes simplex virus type 1 (HSV-1). Our plan is to assess this role through manipulation of virus envelope and host cell membrane composition followed by assay of virus infectivity. Alteration of cell membrane properties will be achieved through use of mutant human cell lines known to harbor genetically-determined membrane defects and through biochemical modification techniques involving incorporation of lipid analogues and specific fatty acids. Work with mutant cell lines represents an extension of preliminary experiments which show a decreased productivity of HSV in skin fibroblasts derived from patients with Duchenne's muscular dystrophy. We plan also to determine the effect of HSV infection on the lipid composition of host cell membranes and to continue work that we have begun on the viral stimulation of phosphatidylinositol turnover. Since membrane fluidity is an important physical parameter of the state of the lipid bilayer, we shall also follow the influence of HSV infection on it by means of spin-labeling. This will be carried out on lipid modified cells, as well. The results of these studies should shed new light on the determination of host range, tissue preference, and individual susceptibility in virus infection and, possibly, provide new avenues for the development of drugs effective against enveloped viruses.